The kinetics of (18)F-FDG in lung cancer: compartmental models and voxel analysis

Background: The validation of the most appropriate compartmental model that describes the kinetics of a specific tracer within a specific tissue is mandatory before estimating quantitative parameters, since the behaviour of a tracer can be different among organs and diseases, as well as between primary tumours and metastases. The aims of our study were to assess which compartmental model better describes the kinetics of 18F-Fluorodeoxygluxose(18F-FDG) in primary lung cancers and in metastatic lymph nodes; to evaluate whether quantitative parameters, estimated using different innovative technologies, are different between lung cancers and lymph nodes; and to evaluate the intra-tumour inhomogeneity. Results: Twenty-one patients (7 females; 71 ± 9.4 years) with histologically proved lung cancer, prospectively evaluated, underwent 18F-FDG PET-CT for staging. Spectral analysis iterative filter (SAIF) method was used to design the most appropriate compartmental model. Among the compartmental models arranged using the number of compartments suggested by SAIF results, the best one was selected according to Akaike information criterion (AIC). Quantitative analysis was performed at the voxel level. K1, Vb and Ki were estimated with three advanced methods: SAIF approach, Patlak analysis and the selected compartmental model. Pearson's correlation and non-parametric tests were used for statistics. SAIF showed three possible irreversible compartmental models: Tr-1R, Tr-2R and Tr-3R. According to well-known 18F-FDG physiology, the structure of the compartmental models was supposed to be catenary. AIC indicated the Sokoloff's compartmental model (3K) as the best one. Excellent correlation was found between Ki estimated by Patlak and by SAIF (R2 = 0.97, R2 = 0.94, at the global and the voxel level respectively), and between Ki estimated by 3K and by SAIF (R2 = 0.98, R2 = 0.95, at the global and the voxel level respectively). Using the 3K model, the lymph nodes showed higher mean and standard deviation of Vb than lung cancers (p < 0.0014, p < 0.0001 respectively) and higher standard deviation of K1 (p < 0.005). Conclusions: One-tissue reversible plus one-tissue irreversible compartmental model better describes the kinetics of 18F-FDG in lung cancers, metastatic lymph nodes and normal lung tissues. Quantitative parameters, estimated at the voxel level applying different advanced approaches, show the inhomogeneity of neoplastic tissues. Differences in metabolic activity and in vascularization, highlighted among all cancers and within each individual cancer, confirm the wide variability in lung cancers and metastatic lymph nodes. These findings support the need of a personalization of therapeutic approaches

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66–19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64–57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9–10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients

Geometry and field theory in multi-fractional spacetime

We construct a theory of fields living on continuous geometries with fractional Hausdorff and spectral dimensions, focussing on a flat background analogous to Minkowski spacetime. After reviewing the properties of fractional spaces with fixed dimension, presented in a companion paper, we generalize to a multi-fractional scenario inspired by multi-fractal geometry, where the dimension changes with the scale. This is related to the renormalization group properties of fractional field theories, illustrated by the example of a scalar field. Depending on the symmetries of the Lagrangian, one can define two models. In one of them, the effective dimension flows from 2 in the ultraviolet (UV) and geometry constrains the infrared limit to be four-dimensional. At the UV critical value, the model is rendered power-counting renormalizable. However, this is not the most fundamental regime. Compelling arguments of fractal geometry require an extension of the fractional action measure to complex order. In doing so, we obtain a hierarchy of scales characterizing different geometric regimes. At very small scales, discrete symmetries emerge and the notion of a continuous spacetime begins to blur, until one reaches a fundamental scale and an ultra-microscopic fractal structure. This fine hierarchy of geometries has implications for non-commutative theories and discrete quantum gravity. In the latter case, the present model can be viewed as a top-down realization of a quantum-discrete to classical-continuum transition.Comment: 1+82 pages, 1 figure, 2 tables. v2-3: discussions clarified and improved (especially section 4.5), typos corrected, references added; v4: further typos correcte

Metabolic Rate of glucose (MRglu) but not standardized uptake value (SUV) can distinguish high risk from low risk uveal melanoma: experience in 20 patients

Aim: Uveal melanoma, the most common primary malignant intraocular tumour, is classified as epithelioid, mixed, and spindle cell type. Based on histopathology, tumours can be divided in high risk (HR, epithelioid and mixed cell type) with worse prognosis, and low risk (LR, spindle cell type) with better prognosis. Up to now, no data exist on the role of 18F-FDG-PET-CT for evaluating the metabolic rate of glucose (MRglu) in these three distinct histological type. Aims of our study were: 1) to assess the feasibility to obtain MRglu (ml/min/100gr) from dynamic 3D 18F-FDG-PET-CT and 2) to evaluate whether epithelioid, mixed, and spindle cell type have different rate of MRglu and/or different SUV values. Materials and Methods: Twenty patients (mean age 62.4± 14 years, 16 M) with large uveal melanoma candidate for surgery underwent ophthalmologic examination, ocular ultrasonography(US), metastatic work-up, and pre-operative dynamic 18F-FDG-PET-CT (185 MBq, PhilipsGXL). 18F-FDG-PET-CT data were analysed semi-quantitatively with SUV, and quantitatively with MRglu. ROIs were drawn over the lesion and over carotid artery for input function. ANOVA test was used for statistical analysis; correlations between SUVmax, SUVmean, MRglu, and tumour volume were also performed. Results: All melanoma (n=20) were visualised at 18F-FDG-PET-CT. The mean value of tumour volume, SUVmax, SUVmean, MRglu were: 1.15± 1.1cc3, 3.34± 1.53, 4.08± 1.94, and 23.73± 14.61ml/min/100gr, respectively. Histopathology proved: 6 epithelioid, 7 mixed, and 7 spindle cell type. Epithelioid and mixed cell type showed significant higher value only in MRglu parameter when compared with spindle cell type: p=0.008 and 0.03 respectively. No significant difference was found between epithelioid and mixed cell type in volume, SUVmax, SUVmean, and MRglu values. According to the risk level, MRglu was significant lower (p<0.013) in LR (n=13) when compared with HR (n=7): 29.4±14.2 mg/min/100gr vs 13.2±8.6mg/min/100gr, while no significant difference was found in SUV values. No correlation was found between SUV and MRglu, SUV and volume, and MRglu and volume. Conclusions: 18F-FDG-PET-CT is a sensitive technique to detect large uveal melanoma and dynamic acquisition allows to easily obtain MRglu. Our results show that epithelioid and mixed cell type uveal melanoma both including epithelioid cells, considered at high risk, have higher glucose consumption than spindle type, without epithelioid cells and considered at low risk. This behaviour is well expressed by different values of MRglu, which gradually increase with increasing malignancy. This finding is not revealed by SUV, which is an “estimate” of glucose consumption, but only by MRglu because it reflects the “real” glucose consumption

Correlation of Tc-99m-red blood cell phleboscintigraphy with clinical severity of chronic venous disease

Equilibrium red blood cell phleboscintigraphy of the lower limbs for the diagnostic management of chronic venous disease has been proposed. The aim of this study was to verify the correlation of the phleboscintigraphic assessment of chronic venous disease with the clinical grading of the severity of the disease, since other diagnostic modalities have been recently demonstrated a poor and only partial correlation. Equilibrium Tc-99m-red blood cell phleboscintigraphy was performed in 27 patients with chronic venous disease. Scintigraphic images of 52 limbs were classified according to a four-class qualitative grading of the severity of the venous disease, and a quantitative scintigraphic index (saphena /femoral ratio) was assigned to each limb. The scintigraphic qualitative grading showed a highly significant correlation with the clinical grading (Rs=0.82, p<0.01), a good interobserver and intraobserver agreement (86.5% and 92.3%, respectively) and more than 90% sensitivity and specificity to identify the categories "minimal or no chronic venous disease" or "more significant disease" (assessed according to the Bayes theorem). Sensitivity and specificity results for the quantitative assessment were not as good. Phleboscintigraphy correlates well with the clinical grading of the severity of chronic venous disease of the lower limbs and may have potential as a valuable diagnostic tool for the noninvasive assessment of chronic venous disease

Rhinoscintigraphy. A simple radioisotope technique to study the mucociliary system

Purpose: This was a radioisotope study of nasal mucociliary clearance of total and subtotal nasal obstruction. Methods: Rhinoscintigraphy was performed by insufflating 1.85 MBq (69 mCi) Tc- 99m MAA in 20 patients. Six cases were regarded as the control group, because the presence of small spurs does not affect nasal patency. The remaining 14 patients had various rhinopathic conditions. Two regions of interest were selected, one in the nasal cavity and one in the pharynx. Mucociliary transport speed was calculated. Results: This parameter appeared to be a sensitive index for the assessment of the degree of mucociliary alteration. It showed that polyposis impairs mucociliary transport most severely, thus confirming the results of other published studies. Conclusions: Rhinoscintigraphy proved to be a reliable, easily reproducible, and harmless method, so it may be used for follow-up examinations in patients who have had surgery of the nose and paranasal sinuses, and for drug therapy of rhinopathic conditions

Assessment of sympathetic innervation of the heart in diabetes mellitus using 123I-MIBG

Radio-labeled metaiodobenzylguanidine (MIBG) is considered an established sympathetic neuron imaging agent capable of scintigraphically visualizing the organs richly innervated by the sympathetic nervous system. Its clinical applications now include cardiac and pulmonary adrenergic imaging. The quantitative determination of global and/or regional abnormalities of MIBG heart uptake has been demonstrated to be very useful in several clinical settings representing one of the major determinants of adverse prognosis. The presence and the severity of autonomic neuropathy are known as important prognostic factors in patients with diabetes. MIBG scintigraphy is able to non-invasively assess and characterize the adrenergic abnormalities of the cardiac innervation also in these patients. In order to evaluate whether 123I-MIBG is able to reveal abnormalities of myocardial adrenergic function in different groups of diabetic patients, we performed 123I-MIBG scintigraphy in control subjects and in normotensive Type 1 diabetic patients with and without autonomic neuropathy (N+ and N- patients), selected according to results of cardiovascular reflex tests, Regional abnormalities of adrenergic innervation were revealed in 10% of control subjects, in 70% of N- patients and in 100% of N+ patients. The finding of a higher than expected prevalence of MIBG regional abnormalities in patients without signs or symptoms of autonomic neuropathy allows to hypothesize that cardiac autonomic nervous damage occurs earlier than previously known in diabetic patients whose cardiovascular tests are still completely normal. (C) 2000, Editrice Kurtis